Daratumumab Combination Lengthened PFS for Heavily Pretreated Myeloma

Adding the CD38-targeting monoclonal antibody daratumumab to bortezomib and dexamethasone resulted in significantly improved progression-free survival (PFS) in patients with heavily pretreated multiple myeloma compared with treatment with bortezomib and dexamethasone alone, according to the results of an interim analysis of a phase III trial published in the New England Journal of Medicine.

Patients assigned to daratumumab had about a 61% lower risk for disease progression and death. However, the three-drug combination was also associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone.

“In the daratumumab group, deep, rapid, and durable responses were reported, with the rates of very good partial response or better and complete response or better approximately double those in the control group,” wrote researchers led by Antonio Palumbo, MD, University of Turin, Italy. “The median duration of response and time to subsequent anti-myeloma therapy were shorter in the control group than in the daratumumab group, which suggests that patients who received daratumumab were also able to maintain longer periods of remission.”

The phase III trial included 498 patients with relapsed or refractory disease who received bortezomib plus dexamethasone with or without daratumumab. The primary endpoint was PFS. These results were presented earlier this year at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.

The researchers conducted a prespecified interim analysis and found that patients assigned daratumumab had significantly longer PFS compared with patients assigned to bortezomib and dexamethasone. The 12-month PFS was 60.7% for the daratumumab group compared with 26.9% for patients in the control group.

With a median follow-up of 7.4 months, the median PFS was not reached for the daratumumab group and was 7.2 months for bortezomib and dexamethasone alone (hazard ratio, 0.39; 95% CI, 0.28–0.53; P < .001).

Patients assigned to daratumumab had an overall response rate of 82.9% compared with 63.2% in the control group (P < .001). A greater percentage of patients in the daratumumab group had very good partial response (59.2% vs 29.1%; P < .001) and complete response (19.2% vs 9%; P = .001). Greater PFS occurred across all subgroups examined, including those patients whose disease was previously treated with bortezomib.

The researchers noted that “because of the relatively short follow-up period, we could not assess whether the addition of daratumumab to bortezomib and dexamethasone confers an overall survival benefit. The final analysis of overall survival will be confounded by the treatment effects of daratumumab in the control group because patients in the control group were allowed to receive daratumumab after the interim analysis was completed.”

A little less than one-half of patients (45.3%) in the daratumumab group reported infusion-related reactions, most of which were grade 1 or 2. The most common grade 3 or 4 adverse reactions in the daratumumab and control groups were thrombocytopenia (45.3% vs 32.9%), anemia (14.4% vs 16%), and neutropenia (12.8% vs 4.2%).